PROJECT SUMMARY During young adulthood, drinking dramatically increases, with binge-level drinking peaking at age 22 and nearly half of individuals reporting binge-level alcohol use. Frequent binge alcohol use during the protracted neuromaturation spanning into the mid-20s may result in greater brain and cognitive effects than similar alcohol use in later adulthood. In response to RFA-AA-17-003, this application proposes a Research Project Site of the National Consortium on Alcohol and Neurodevelopment in Adolescence second phase (NCANDA-2) to determine the predictors and effects of heavy adolescent alcohol use in adolescence and young adulthood. To achieve this, the Duke site of NCANDA-2 will continue to follow a cohort of 175 in the Raleigh-Durham, NC area (n=831 across all 5 sites) participants (ages 12-21 at baseline first visit) to acquire the necessary data to advance our understanding of adolescent development and the effects of alcohol use during adolescence on the adult brain. NCANDA-2 will use multimodal neuroimaging, cognitive testing, behavioral assessment, biospecimen collection, and multimodal assessments in the natural environment. The examination of alcohol consequences will focus on structural and functional maturation of brain areas that actively develop during adolescence and young adulthood, are involved in psychological regulation, respond to rewards, and appear vulnerable to neurotoxic effects of alcohol. In addition, the UCSD site will collaborate with the Duke and OHSU sites to study recovery of these abnormalities. Specifically, we will examine the degree to which targeted heavy drinking related neurocognitive and brain integrity deficits remit over 4 weeks of monitored abstinence. Duke will also collaborate with the Pittsburgh site to examine the influence of alcohol use on reward and inhibitory systems with longitudinal analyses of a rewarded antisaccade task to evaluate changes in these systems for youth who increase drinking versus those who do not. Sex differences in development, alcohol use patterns and history, impact of alcohol use on the brain, and sex-differentiating psychosocial factors (e.g., depression symptoms) will be considered in analyses. With the additional longitudinal data provided by this renewal, we will determine the effects of alcohol exposure on the developmental trajectory of the adolescent human brain, and identify preexisting psychobiological vulnerabilities and resiliencies that may alter adolescents? and young adults? risk for alcohol or other substance use disorder and other mental health and developmental outcomes.